| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with advanced non-small cell lung cancer |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate progression-free survival (PFS) of MetMAb + erlotinib, relative to erlotinib + placebo, in patients with Met-high tumors (as determined by immunohistochemistry), as well as in the "overall" patient population |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate PFS in patients with squamous cell histology
•To determine the overall RECIST response rate and duration of response in patients with Met high tumors, squamous cell histology, as well as in the "overall" patient population
•To characterize the safety and tolerability of MetMAb + erlotinib in patients with non small cell lung cancer (NSCLC)
•To evaluate minimum concentration (Cmin) and maximum concentration (Cmax) of both MetMAb and erlotinib in patients with NSCLC
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MetMAb STUDY OAM4558g
Protocol number : OAM4558g (DNA substudy)
Date Final: 18 November 2008 |
|
| E.3 | Principal inclusion criteria |
Patients must meet the following criteria for study entry:
•Signed, written informed consent prior to any study-specific screening procedures
•Age ≥ 18 years of age
•ECOG performance status of 0, 1, or 2 (see Appendix D of the protocol)
•Histologically confirmed NSCLC; following accrual of the first 120 histologically unspecified "overall"
population, the subsequent 50 patients must have squamous cell histology
Availability at the site of a representative formalin-fixed, paraffin-embedded tumor specimen that enabled the
definitive diagnosis of NSCLC with adequate viable tumor cells in a tissue block (preferred) or 15 unstained,
serial slides, accompanied by an associated pathology report is required prior to randomization. Cytological or
fine-needle aspiration samples are not acceptable. If the archival tissue is neither sufficient nor available, the
patient may still be eligible, upon discussion with the Medical Monitor, assuming the patient:
Can provide at least ≥ 5 unstained, serial slides
or
Is willing to consent to and undergo a pre-treatment core or excisional biopsy of the tumor. Cytological or fineneedle
aspiration samples are not acceptable.
•Recurrent or progressive disease following at least one chemo containing regimen for Stage IIIB/IV disease
Patients who receive neo-adjuvant and/or adjuvant therapy for Stage I-IIIa disease prior to their first-line regimen
(for Stage IIIb/IV) are eligible for study participation, provided they also receive first-line therapy for Stage IIIb/
IV disease
At least one of the chemotherapy containing regimens (for any stage) must have been platinum-based
•Measurable disease in accordance with RECIST 1.0 (see Appendix C of the protocol)
•At least one measurable lesion on a pre-treatment FDG-PET scan that is also a target lesion on CT according to
RECIST 1.0 (as determined by the site)
Throughout the course of this study, an Image Reading Facility (IRF) will evaluate FDG-PET results and together
with the sponsor will determine whether FDG-PET imaging should continue in all participating sites or whether FDG-PET imaging should be confined to a few sites based on the quality of the data received. Therefore, this criterion may only apply to sites that will continue to perform FDG-PET imaging (see protocol Section 4.5.6).
•Use of an acceptable means of contraception for men and women of childbearing potential |
|
| E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from study entry:
•More than two prior treatments for Stage IIIB/IV
A change of chemotherapy regimen for reasons of patient intolerance or excessive toxicity does not constitute an additional regimen, unless disease progression was documented at the time of treatment change.
Combined treatment with chemotherapy and radiation constitutes a single prior regimen
Surgery does not constitute a prior regimen
•More than 30 days of exposure to an investigational or marketed agent that can act by EGFR inhibition, or a known EGFR-related toxicity resulting in dose modifications
EGFR inhibitors include (but are not limited to) gefitinib, erlotinib, and cetuximab
•Chemotherapy, biologic therapy, radiotherapy or investigational drug within 28 days prior to randomization
Exceptions are kinase inhibitors, which may be used within 2 weeks prior to randomization, provided that any drug-related toxicity has adequately resolved and prior approval has been obtained from the Medical Monitor
•Untreated and/or active (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) CNS metastasis
Patients with history of brain metastasis may be eligible for study participation, as long as they meet the following criteria:
Measurable disease outside the CNS, as defined by RECIST
No radiographic evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
Adequate CNS-directed treatment, which may include neurosurgery or stereotactic radiosurgery.
The screening of CNS radiographic study is ≥ 4 weeks since completion of radiotherapy and ≥ 2 weeks since the discontinuation of corticosteroids and anticonvulsants
Radiotherapy and/or stereotactic radiosurgery must be completed ≥4 weeks prior to Day 1
Neurosurgery must be completed ≥ 24 weeks prior to Day 1, and brain biopsy must be completed ≥ 12 weeks prior to Day 1
•History of serious systemic disease within the past 6 months prior to randomization, including myocardial infarction, uncontrolled hypertension (persistent blood pressure > 150/100 mmHg on antihypertensives), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or Grade II or greater peripheral vascular disease
•Uncontrolled diabetes as evidenced by fasting serum glucose level > 200mg/dL
•Major surgical procedure or significant traumatic injury within 28 days prior to randomization
•Anticipation of need for a major surgical procedure during the course of the study
•Local palliative radiotherapy within 7 days prior to randomization or persistent adverse effects from radiotherapy that have not been resolved to Grade II or less prior to randomization
•Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting gastrointestinal absorption
•Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinical significant hypercalcemia are eligible
•Any of the following uncorrected abnormal hematologic values (within 2 weeks prior to randomization)
ANC < 1,500 cells/µL
Platelet count < 100,000 cells/µL
Hemoglobin < 9.0 g/dL
•Other baseline laboratory values (within 2 weeks prior to randomization)
Serum bilirubin > 1.5 X ULN
Alkaline phosphatase, AST and ALT > 2.5 ULN
Serum creatinine > 1.5 X ULN
Uncontrolled hypercalcemia (> 11.5 mg/dL or > 1.5 ionized calcium)
•Pregnant or breastfeeding women
•Other malignancies that have undergone a putative surgical or radiotherapy cure (specifically, intraepithelial carcinoma of the cervix uteri, localized prostate cancer post prostatectomy, or basal/squamous cell carcinoma of the skin) within 5 years prior to randomization may be discussed with the Medical Monitor.
•Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient’s understanding of the Informed Consent Form
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| -Median Patient Free Survival (PSF) for each treatment arm |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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